A Multi-arm Phase I Trial of Hepatic Arterial Infusion of Irinotecan With 1) Systemic Bevacizumab 2) Systemic Bevacizumab and Oxaliplatin 3) Systemic Bevacizumab and Cetuximab in Patients With Advanced Cancers Metastatic to the Liver
The Study Drugs:
Irinotecan is designed to stop cancer cells from making new DNA (the genetic material of
cells). This may cause cancer cells to die.
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the
growth of blood vessels that supply nutrients necessary for tumor growth.
Oxaliplatin is designed to block new cancer cells from growing.
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking
proteins inside cancer cells.
Study Arms and Dose Levels:
If you are found to be eligible to take part in this study, your doctor will assign you to a
study arm. Your study arm will depend on the type of cancer, your KRAS test result (if
applicable), and the drugs you have taken in the past.
- If you are in Arm A, you will receive irinotecan and bevacizumab.
- If you are in Arm B, you will receive irinotecan, bevacizumab, and oxaliplatin.
- If you are in Arm C, you will receive irinotecan, bevacizumab, and cetuximab.
The dose that you receive will depend on when you are enrolled in this study and the safety
data that is available at that time. The first set of 3-6 participants to join each study
arm will receive the lowest dose of the drug combination. The next set of 3-6 participants
will receive a higher dose of the drug combination. Each new set of participants will
receive a higher dose than the group before it, if no intolerable side effects were seen.
This will continue until the highest tolerable dose of the drug combinations is found.
Once the highest tolerable dose is found for each arm, 14 participants with the tumor type
that has responded well to a particular study drug combination will receive the study drugs
at that dose level. These participants will be in the "expansion" arms.
You will be hospitalized to receive the study drug combination. The morning after you enter
the hospital, you will have a catheter placed in your right groin area. A catheter is a
sterile flexible tube. It will be placed into a large artery (the blood vessel that carries
blood to your liver) while the area is numbed with local anesthetic. Your doctor will
explain this procedure to you in more detail, and you will be asked to sign a separate
consent form for it.
After you return to your room, you will receive irinotecan as described below.
Study "cycles" will be repeated every 28 days. The catheter will be placed and removed
during each cycle. Each time, you will lie in bed for the entire time that the catheter is
in place. While the catheter is being removed, the study staff will apply pressure to your
groin area for 15 minutes to stop the bleeding.
Study Drug Administration:
Irinotecan will be given through the catheter into your liver artery, continuously for
48hours (Days 1 through 2 of each cycle). Before every irinotecan dose, you will also
receive drugs by vein to lower the risk of nausea, if your doctor thinks this is needed for
Bevacizumab will be given by vein once every 2 weeks. The first time you receive
bevacizumab, it will be given over 90 minutes. If you tolerate it well, all other
bevacizumab doses will be given over 30-60 minutes.
Oxaliplatin, if you receive it, will be given by vein over 2 hours once every 2 weeks.
Before every oxaliplatin dose, you will also receive drugs by vein to lower the risk of
nausea, if your doctor thinks this is needed for routine care.
Cetuximab, if you receive it, will be given by vein once every 2 weeks. The first time you
receive cetuximab, it will be given over 2 hours. All other cetuximab doses will be given
over 1 hour.
If you do not tolerate the study drug combination well, the doses that you receive may be
lowered. If you experience certain side effects, your study drug doses may be delayed and
the study cycle may be longer than 28 days.
You will be given standard drugs (heparin and diphenhydramine) to help decrease the risk of
side effects. You may ask the study staff for information about how the drugs are given and
You will be in the hospital for about 5-7 days at the beginning of every cycle, until you
recover from side effects that may occur. You will be seen by a doctor or "advanced
practice" nurse every day while you are in the hospital.
At the beginning of each cycle and then once a week during each cycle, blood (about 1
tablespoon) will be drawn for routine tests. At the beginning of each cycle and then once
every 4 weeks (or earlier if needed), you will have a physical exam.
You will have scans such as a chest x-ray, CT, MRI, and/or PET scan after every 2 cycles (8
weeks) or earlier if the study doctor thinks it is in your best interest, or the cancer gets
worse. These scans are to check the status of the disease. If the study doctor thinks it
is more appropriate for you, other types of scans may need to be performed. The study
doctor will discuss these scans with you, and you may be asked to sign a separate consent
Additional Tests/Procedures for Some Participants:
If you experience severe diarrhea and/or low white blood cell counts while on this study,
blood (about 2 teaspoons) will be drawn to test your DNA to find out if you may be at a
higher risk of side effects from irinotecan. If the test shows that you may have a higher
risk, then you will receive irinotecan at a lower dose level.
If you are in Arm C (which as discussed above, does not include colorectal cancer patients
with a KRAS mutation), a leftover sample of tumor tissue will be tested for the KRAS
mutation. If no leftover tumor tissue from an earlier procedure is available, and if your
KRAS status is unknown, you will have a needle biopsy of a tumor performed. The tissue will
be tested for the KRAS mutation. This procedure will be done on an appropriate tumor area
that is able to be biopsied, and it may or may not be the liver tumor. This will be the
Length of Study:
You may stay on study for as long as the disease has not gotten worse, the cancer has not
gone away completely, and you have not experienced intolerable side effects. In any of
those cases, you would be taken off study.
About 28 days after your last dose of study drugs, you will have an end-of-study visit. At
this visit, the following tests and procedures may be performed:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have an x-ray, CT scan, PET scan, or MRI
scan to check the status of the disease.
This is an investigational study. It is investigational to give irinotecan into a liver
artery. The study drug combinations and dose levels are also investigational.
The study drugs are commercially available and FDA approved to treat the following:
- Irinotecan by vein -- colorectal cancer that is metastatic (has spread).
- Bevacizumab -- metastatic colorectal cancer, breast cancer, non small-cell lung cancer,
and a type of brain cancer called glioblastoma multiforme.
- Cetuximab -- colorectal cancer, and head and neck cancer.
- Oxaliplatin -- colorectal cancer.
Up to 140 patients will take part in this study. All will be enrolled at M. D. Anderson.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Doses (MTDs)
Evaulated with each 28 day cycle
Apostolia M. Tsimberidou, MD, PhD
UT MD Anderson Cancer Center
United States: Institutional Review Board
|UT MD Anderson Cancer Center||Houston, Texas 77030|